Following this thread with interest, as I've had this issue crop up over the years across different systems. The last comment above rings true.
I'm dealing with fewer variables in some ways, as the cost of my gear hasn't justified investing in high end cables or power conditioners. Being on the lower end of the gear food chain I'm focused on bang-for-the-buck, as I work with the givens of the space- no possibility for a listening-only sound room.
First experience early on- Heresy's and '70's transistor preamp/amp (apt holman). Screechy, thin, even while room is absorbent.
Second, Cornwalls and vintage tubes (Scott, then Eico HF-81, then Anthem Integrated 1). High's tamed, now bass bloat's the issue, probably due in part to low damping factor of amps.
Started then on a rebuilt Quad ESL57-based system in LR; screech/bass bloat issues gone. Now happily working within those speakers' limitations in that space, tube rolling with a Rogue Atlas. A real late-evenings with rye on rocks system, built for sitting still in the sweet spot.
In a new workplace system I started with Altec 604G's in 620 cabinets driven by the old HF-81. Live space. Pretty good, but highs somewhat forward and harsh. Switched to Alan Eaton SET45 integrated a few days ago. Paint started peeling- the more extended bandwidth of the new amp emphasized the speakers' treble issues, and the better control of the woofer thinned out the bass, but probably made it more accurate (BTW 1.5 watts is enough!). I still suspect the combination of this amp and speakers could be great, so am investing in Jagusch crossovers that address the well known limitations of the stock crossovers (on order, may come next week).
In yet another system (in home/workplace) in a very live medium large space I've run old Monitor Audio MA-3 II 3-way speakers on custom-built Audio Note style stands (steel with lead shot). Powered by the Anthem (push-pull, with 4 EL84's per channel) it's proved extremely listenable. Earlier speaker attempts included Vandersteen II's- really veiled and laid-back. Then Snell E's- sounded like more like boxes than music. Paid a bit more for the Monitor Audios than for the Vandersteens (still only $500), but right off the bat they just sounded right. Smooth across the frequency spectrum, forgiving with mediocre recordings, revealing and tonally compelling with good ones. Then the amp caught fire after being left alone for a few months, due to a malfuctioning tube (sovtek, no fuses in amp). Switched in an old Bedini 25/25 (Transistor class A) that was OK with the Quads- but back to "thin and harsh"! Suspected degraded caps, had those fixed. Better, but I still strained to enjoy the music. Yesterday I got the Anthem back from the shop. Wow- everything's right again. Even with the terrible acoustics of the space, the music takes the tension out of my muscles instead of cranking it up. While this amp hasn't got much of a reputation (not hand-wired, not SET, small output transformers, clunky non-vintage look), it's been a real sleeper for me, playing pretty well to great with the wide variety of types of speakers tried with it, including the picky Quads.
In yet another system (vacation home), I had a heavily modded MAC 5100 integrated paired with ADS 810's. Sounded great, until it crapped out. Tried to get it repaired locally in NH- a good tech said without a schematic describing the mods he wouldn't know where to start- an idiosyncratic set of cap and transistor replacements had been soldered around and over the originals, sometimes also totally replacing them. A real homebrew job. So I sent it off Audio Classics, who restored it to factory condition. Would you believe it? Now the ADS's sound thin and bright. Ugh. Hoping break-in will take care of this.
Clear take-aways?
If you can't change room acoustics much, the combination and interaction of amp and speakers is key. And the particulars of which amp and which speakers has a lot to do with it. While it's still clear to me that changes at the source/output locations are most consequential (eg the huge difference between a Shibata and a conical stylus), with accumulated experience it's clear how important the right (not the most expensive) power amp is.
Trusting your ears to know what's right when you hear it is crucial as well. I taught color printing for years- no two sets of eyes are alike; we all see color differently. Same with ears. Resist substituting others' experience for yours. My kids can hear 15hz clearly. I don't anymore.
I seek different experiences in my various room/system setups and enjoy learning from these variations. Maybe some day I'll reach beyond DH Labs and Blue Jeans cables and go interconnect crazy, but with the number of systems I run, that seems just a bit too high on the curve of diminishing returns for it to be worth the trouble. For the harsh/thin/bright issue working backwards from the amp/speaker combination is the best way to go, in my limited experience.
